Infectious Disease · Medical Literature
[Comment] Temocillin as a carbapenem-sparing option for ESBL bloodstream infection
Abstract
Antimicrobial resistance is a global threat to public health, already associated with more than 1 million attributable deaths per year; Enterobacterales, including Escherichia coli, are the pathogens responsible for the largest numbers of these antimicrobial resistance-associated deaths.1 Resistance to third-generation cephalosporins, most commonly mediated by extended-spectrum ß-lactamase (ESBL) production, is rising rapidly2 and is associated with a particularly high incremental risk of death.
Clinical relevance
Does temocillin represent a safe and effective carbapenem-sparing option for targeted treatment of bloodstream infections caused by third-generation cephalosporin-resistant Enterobacterales (3GCR-E), in light of the landmark ASTARTÉ randomised controlled trial? __SNAPSHOT__ {"studyDesign":"Published correspondence/editorial commentary (Lancet Comment) contextualising findings from the ASTARTÉ trial — a multicentre, phase 3, open-label, non-inferiority, randomised, pragmatic, investigator-initiated clinical trial (Cogliati Dezza et al., Lancet, July 9, 2026; DOI: 10.1016/S0140-6736(26)00760-9)","setting":"29 hospitals in Spain (ASTARTÉ trial); commentary authors affiliated with the University of Toronto and Sunnybrook Health Sciences Centre, Canada","sampleSize":"ASTARTÉ trial: n=334 (temocillin: n=167, carbapenem: n=167); modified ITT population: n=328 (temocillin: n=163, carbapenem: n=165)","population":"Adults aged ≥18 years with monomicrobial bacteraemia caused by Enterobacterales resistant to third-generation cephalosporins (cefotaxime, ceftriaxone, or ceftazidime) and susceptible to both meropenem and temocillin, requiring at least 4 days of active intravenous antibiotic therapy; screened from 2,420 patients with Enterobacterales bacteraemia","intervention":"Intravenous temocillin 2 g every 8 hours (30–40-minute infusion) as targeted therapy","comparator":"Intravenous meropenem 1 g every 8 hours (15–30-minute infusion), or ertapenem 1 g once daily if deemed clinically appropriate","primaryOutcome":"Clinical success at test-of-cure visit, defined as resolution of all new signs and symptoms related to the index infection, no need to stop or change the study drug due to an adverse event or clinical failure, no recurrence through day 28, and survival at day 28","followUp":"28 days","fundingSource":"Instituto de Salud Carlos III (Spanish government health research agency); investigator-initiated trial"}
Key findings
In the modified intention-to-treat population of the ASTARTÉ trial (the primary evidence base contextualised by this Commentary), clinical success was achieved in 74% of patients in the temocillin group versus 73% in the carbapenem group. The absolute difference in clinical success was 0.3 percentage points (one-sided 95% CI: −7.7 to ∞; p=0.017), meeting the pre-specified non-inferiority margin of 10%. The probability that a temocillin-treated patient had a better Desirability of Outcome Ranking (DOOR) than a carbapenem-treated patient was 50.4%, indicating essentially equivalent composite clinical outcomes across the two arms. The rates of adverse events (AEs) and serious AEs did not differ significantly between groups, although numerically more AEs were reported in the temocillin arm (specific frequencies not extractable from the abstract or Commentary alone). This represents the first randomised controlled trial to demonstrate non-inferiority of any alternative agent to carbapenems for bacteraemia caused by 3GCR-E. Of 2,420 patients screened, 464 were excluded because of temocillin-resistant isolates, underscoring that susceptibility testing is an absolute prerequisite before temocillin use. Treatment duration ranged from 7 to 14 days, with sequential oral therapy permitted from day 5 onward. The commentary authors emphasise the broader public health significance: carbapenems are currently the standard of care for 3GCR-E infections, and their overuse is driving global carbapenem resistance; temocillin, as a narrow-spectrum agent, could reduce this selection pressure. NNT: not calculable from the available data. NNH: not reported.
Practice implications
This Commentary contextualises the ASTARTÉ trial — the first phase 3 RCT to demonstrate that a non-carbapenem agent (temocillin) is non-inferior to carbapenems for targeted treatment of 3GCR-E bacteraemia. What the trial established: temocillin is an effective and safe targeted therapy option in adults with susceptible monomicrobial 3GCR-E bacteraemia who require at least 4 days of IV therapy, in a Spanish multicentre hospital setting. What the trial did not establish: efficacy in polymicrobial bacteraemia; empirical use (susceptibility must be confirmed); utility in patients with infections typically requiring >14 days of therapy (endocarditis, prosthetic joint infection, meningitis); performance in carbapenemase-producing organisms or temocillin-resistant strains (19% of screened patients had temocillin-resistant isolates); performance in ICU or immunocompromised populations (not well characterised in available abstract data). Generalisability is constrained by the single-country (Spain) design, open-label methodology, and the fact that temocillin is not approved in the United States (FDA approval limited to Burkholderia cepacia pulmonary infections) and is only commercially available in Belgium and the United Kingdom. The commentary authors characterise the ASTARTÉ results as 'practice-changing' evidence; however, implementation in jurisdictions where temocillin is unavailable or unlicensed will require regulatory action. The open-label design and slightly longer median treatment duration than currently supported by bacteraemia management evidence are additional caveats. Only the abstract and a secondary commentary were available for this summary; full analysis of subgroup data, safety data tables, and source-stratified outcomes requires access to the primary publication. __LIMITATIONS__ Open-label design: masking was not feasible because the comparator arm included two drugs with different dosing schedules (meropenem vs ertapenem), introducing potential performance and detection bias.,Single-country trial (Spain): limits generalisability to healthcare systems with different ESBL epidemiology, predominant resistance mechanisms, and temocillin availability.,Temocillin not approved in the US and unavailable in many countries, limiting immediate translatability of findings globally.,19% of screened patients were excluded due to temocillin-resistant isolates, emphasising that susceptibility testing is mandatory; clinicians cannot rely on empirical temocillin use.,Patients excluded if they required >14 days of therapy (endocarditis, prosthetic joint infection, meningitis), limiting applicability to complicated or deep-seated 3GCR-E infections.,Open-label investigator-initiated trial with pragmatic design; imbalances in clinical decision-making between arms (e.g., step-down oral therapy choice) cannot be fully excluded.,Median treatment duration was slightly longer than current evidence supports for bacteraemia management, which may have influenced outcome rates.,Immunocompromised patients and critically ill ICU patients were not separately characterised in the available abstract data; prior observational data suggest potentially higher failure rates in these subgroups.,Only abstract-level and secondary commentary data were available for this teaching summary; full safety tables, subgroup analyses (by source of bacteraemia, species, and resistance mechanism), and microbiological outcome data require access to the full publication.,Non-inferiority margin of 10% is clinically meaningful; a residual inferiority of up to 10% cannot be excluded with certainty from the lower bound of the confidence interval (−7.7 percentage points). __BOTTOM_LINE_CATEGORY__ practice_changing __BOTTOM_LINE__ The ASTARTÉ trial — contextualised by this Lancet Commentary — provides the first phase 3 RCT evidence that temocillin is non-inferior to carbapenems for targeted treatment of monomicrobial 3GCR-E bacteraemia in adults with susceptible isolates, achieving clinical success in ~74% vs ~73% of patients with an absolute difference of 0.3 percentage points (one-sided 95% CI: −7.7 to ∞; p=0.017). Clinicians in countries where temocillin is available should consider it a legitimate carbapenem-sparing option in this setting, provided susceptibility is confirmed prior to use and the patient does not have infection types requiring prolonged therapy. Practice adoption globally remains constrained by limited regulatory availability, particularly in the United States, where temocillin is not approved for systemic infections.